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1994 Fiscal Year Final Research Report Summary

Molecular biological approach to the abnormalities of extracelluar matrix of the diabetic nephropathy.

Research Project

Project/Area Number 04671481
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionOkayama University

Principal Investigator

MAKINO Hirofumi  Okayama University Medical School, assistant, 医学部, 助手 (50165685)

Co-Investigator(Kenkyū-buntansha) SHIKATA Kenichi  Okayama University Medical School, assistant, 医学部, 助手 (00243452)
KASHIHARA Naoki  Okayama University Hospital, assistant, 医学部附属病院, 助手 (10233701)
IKEDA Shyuji  Okayama University Hospital, assistant, 医学部附属病院, 助手 (10212771)
NIMOMIYA Yoshifumi  Okayama University Medical School, professor, 医学部, 教授 (70126241)
Project Period (FY) 1992 – 1994
Keywordsdiabetes mellitus / extracellular matrix / kidney / glomerulus / type IV collagen / gene / proteoglycans / immunoelectron microscopy
Research Abstract

Extracellular matrix has been shown to be consisted of collagens, laminins and proteoglycans. In diabetic nephropathy, the altertions of biochemical properties of type IV collagen and the decreased expression of proteoglycans are considered to be major pathological changes of the disease and related to the phenotypic changes of glomerular cells. Immunoelectron microscopic studies of diabetic nepropathy patients with nephrotic syndrome showed the thicking of glomerular basement membranes (GBM), increased amount of type IV collagens with decreased density, and decreased heparan sulfate proteoglycan. These alterations of extracellular matrix components seems to contribute to the the impairment of size and charge barrier of the GBM and proteinuria. Furthermore, we cloned a novel chain of type IV collagen, i.e.alpha4 chain, which cDNA (NK4) included NC-1 domain and expands 1.9 Kb. Northern blot analyzes showed -9.5 Kb transcript. Immunofluorescence studies of alpha1, alpha2, alpha3, alpha4, and basement membrane associated-collagen (BAC) showed alpha1 and alpha2 localized to the glomerular mesangial area and glomerular capillary, while alpha3 and alpha4 localized mainly along the capillary wall. BAC immunoreactivity was observed in the mesangial area. In the kidney of diabetic patients, expanded mesangial matrix and thickened GBM showed increased expression of alpha1-alpha4 chains and BAC.Furthermore, we analyzed the expression of the interstitial collagens, such as III,V,VI collagens. Type III collagen exclusively expressed in the interstinum of the kidney and type V and VI collagens had mesangial expressions. In diabetic kidney, these collagens were increased in the mesangial area.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Makino H et al.: "Ultrastructunl changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy." Laboratory Investigation. 68. 45-55 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hironaka K et al.: "Renal basement membranes by ultrahigh resulution scanning elecron micruscopy." Kidney International. 43. 334-345 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H et al.: "Localization of fibril/microfibril and basement membrance collagen in diabetic glomerulosclerosis in type 2 dinbetos." Diabeti Medicine. 11. 304-311 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H et al.: "Immunoreactivity of the JK-132monoclonal antibody directed agninst basement membranecollagen in normal and diabetic glomeruli." Virclows Ardir. 424. 235-241 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morioka S: "Chnges in plasma concentrations of vitronectin in patients with diabetic nephropathy" Acta Media Okayama. 48. 137-142 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H.: "Molecular biology of regulators of extrucellular matrix in glomerular injyurios." Connective Tissue. 25. 201-216 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H et al.: "GBrowth factors and diabetic nephropathy" Igaku no Ayumi. 171. 575-579 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H.: "Molecular biology of glomerular hypertrophy and sclocrusis.-Mesnngial cells-" Kidney and Dialysis. 37. 679-684 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makino H., et al.: "Ultrastructual changes of extracellular matrices in diabetic nephropathy revealed by high resolution scanning and immunoelectron microscopy." Laboratory Investigation. 68. 45-55 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hironaka K., et al.: "Renal basement membranes by ultrahigh resolution scanning electron microscopy" Kidney International. 43. 334-345 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino H., et al.: "Localization of fibril/microfibril and basement membrane collagen in diabetic glomerulosclerosis in type 2 diabetes." Diabetic Medicine. 11. 304-311 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino H., et al.: "Immunoreactivity of the JK-132 monoclonal antibody directed against basement membrane collagen in normal and diabetic glomeruli." Virchows Archiv. 424. 235-241 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morioka S., et al.: "Changes in plasma concentrations of vitronectin in patients with diabetic nephropathy" Acta Med Okayama. 48. 137-142 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino H: "Molecular biology of regulators of extracellular matrix in glomerular injyuries." Connective Tissue. 25. 201-2-6 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino H., et al.: "Growth factors and diabetic nephropathy." Igaku no Ayumi. 171. 575-579 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Makino H.: "Molecular biology of glomerular hypertrophy and scloerosis. -Mesangial cells-" Kidney and Dialysis. 37. 679-684 (1994)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-16  

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